The human infectious dose 50(HID50) of current H1N1 and H3N2 cold-adapted (ca) reassortant viruses ranges from 10 to the 5.5 to 10 to the 6.5 TCID50. The six internal genes (i.e., genes that code for nonsurface viral proteins) of the ca donor virus reproducibly confer on wild-type viruses (1) satisfactory attenuation, (2) immunogenicity, (3) phenotypic stability, and (4) non-transmissibility. Infection with 70 HID50 of a ca reassortant induced greater resistance to wild-type virus challenge than did inactivated influenza vaccine. The safety, immunogenicity, and HID50 of a human-avian influenza reassortant containing the 6 internal genes of its avian influenza virus parent was determined in seronegative volunteers. The reassortant was satisfactorily attenuated. Vaccinees shed significantly less virus than individuals infected with wild-type virus. Preliminary analysis indicates that the immunogenicity of this virus is similar to that of the cold-adapted reassortants.